Influence of GRIK4 genetic variants on the electroconvulsive therapy response

Several lines of evidence have shown the involvement of the glutamatergic system in the function of electroconvulsive therapy (ECT). In particular, patients with treatment resistant depression (TRD) and chronic depression have lower levels of glutamate/glutamine than controls, and ECT can reverse this deficit. Genetic factors might contribute to modulating the mechanisms underlying ECT. This study aimed to evaluate the relationship between three polymorphisms (rs1954787, rs4936554 and rs11218030) of the glutamate receptor ionotropic kainate 4 (GRIK4) gene and responsiveness to ECT treatment in a sample of one hundred individuals, TRD or depressive Bipolar Disorder patients resistant to pharmacological treatments. The results revealed that GRIK4 variants were significantly associated with the response to ECT. In particular, we found that patients carrying the G allele of the GRIK4 rs11218030 had a significantly poorer response to ECT (p = 2.71 7 10-4), showing five times the risk of relapse after ECT compared to the AA homozygotes. Analogously, patients carrying the GG rs1954787 genotype and rs4936554 A allele carriers presented a double risk of lack of response after ECT (p = 0.013 and p = 0.040, respectively). In conclusion, the current study provides new evidence, indicating that some GRIK4 variants modulate the response to ECT in patients with depression resistant to treatment, suggesting a role for kainate receptor modulation

Seizure adequacy markers and the prediction of electroconvulsive therapy response

Objectives: Electroconvulsive therapy (ECT) is the most effective therapy for patients with treatment-resistant depression; however, some patients do not respond or relapse in a short time. Electroconvulsive therapy stimulus parameters may be related to the outcome. We carried out a retrospective study review to investigate various ECT parameters in relation to the outcome, clinical variables, and pharmacological treatments. Our aim was to understand which factors could be considered putative seizure quality markers and which are relevant to clinical practice. Methods: Two physicians evaluated the seizure length, the postictal suppression index, the wave amplitude, tachycardia, and hemispheric brain wave synchronicity in a double-blind manner for 45 treatment-resistant depression patients receiving ECT. Results: The analysis showed a significant association between the outcome and the ECT seizure quality measured by the parameters (P = 9.9 7 10-5). Among patients with poor-quality seizures, 61.5% relapsed after approximately 1month fromthe last ECT session. Particularly, there was an association between higher symptomatology decrease and higher quality of hemispheric brain wave synchronicity (P = 5.0 7 10-6), as well as a higher wave amplitude (P = 0.01). Conclusions: Our results confirm that ECT seizure quality was strongly correlated with the decrease of depressive symptomatology